Distinct regulatory profiles of interleukins and chemokines in response to cigarette smoke condensate in normal human bronchial epithelial (NHBE) cells.
Bronchial epithelium is frequently exposed to air pollutants, and it is hypothesized that these cells elicit inflammatory responses as early elements in pulmonary defense. Our purpose was to evaluate changes in messenger RNA levels of 84 genes representing cytokines and receptors over a repetitive-exposure time course to further define the inflammatory responses associated with mainstream cigarette smoke (MSS) exposure in an in vitro lung model. Normal human bronchial epithelial cells were treated with mainstream cigarette smoke condensate (CSC) prepared from Kentucky 2R4F cigarettes (60 microg total particulate matter/mL media, 0.2% dimethylsulfoxide), and examined by quantitative real-time polymerase chain reaction. Applications of CSC were designed in seven groups to test immediate, early, intermediate, and late responses evaluated at the end of alternating exposure/recovery periods. Three predominant gene expression responses were observed: adaptive (return to baseline), sustained (maintained expression during treatment), and chronic (maintained expression posttreatment). Overall, 25 genes exhibited statistically significant changes: 14 genes exclusively elevated, 10 genes exclusively depressed, and 1, interleukin-8 (IL8), exhibiting both up- and downregulation in the seven groups. The most responsive genes were osteopontin (34-fold upregulation) and CXCL14 (23-fold downregulation). Our observations suggest that specific genes involved in inflammatory pathways respond to CSC in chronic, sustained, or adaptive patterns with the chronic pattern as the predominant behavior.
Parsanejad
Reza
R
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Fields
Wanda R
WR
Steichen
Thomas J
TJ
Bombick
Betsy R
BR
Doolittle
David J
DJ
D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008297:Male; D053495:Osteopontin / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*; D012906:Smoke / Q000009:adverse effects*; D013638:Tars / Q000633:toxicity*; D014026:Nicotiana / Q000009:adverse effects*; D015854:Up-Regulation
C118056:CXCL14 protein, human; D018925:Chemokines; D019743:Chemokines, CXC; D016209:Interleukin-8; D007378:Interleukins; D012906:Smoke; D013638:Tars; C024746:tobacco tar; D053495:Osteopontin